Calcium-induced calcium release (CICR) describes a biological process whereby calcium is able to activate calcium release from intracellular Ca2+ stores (e.g., endoplasmic reticulum or sarcoplasmic reticulum). Although CICR was first proposed for skeletal muscle in the 1970s, it is now known that CICR is unlikely to be its primary mechanism for activating SR calcium release. Instead, CICR is thought to be crucial for excitation-contraction coupling in cardiac muscle and it is now obvious that CICR is a widely-occurring cellular signaling process present even in many non-muscle cells, e.g. in the insulin-secreting pancreatic beta cells and many other cells. Since CICR is a positive-feedback system, it has been of great interest to elucidate the mechanism(s) responsible for its termination.